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Drugline nr 14183

Publicerat 1997-05-09

Question

Treatment with labetalol/felodipine and breast-feeding.

Clinical background: A woman with essential hypertonia is treated with labetalol (Trandate), 900 mg/day and felodipine (Plendil), 30 mg daily. In pregnancy week 30 she delivered a premature baby. If the labetalol dose to the mother is over 300 mg/day, as in the present case, the milk will be freezed until the baby is fully developed. Could the baby be breast-fed when the baby is fully developed with regard to the high dose of labetalol? Is there any risk breast-feeding during felodipine treatment?

Answer

Labetalol is excreted into breast milk (1).

In three lactating women (2) with pregnancy hypertension, 6-9 days post partum, the transfer of labetalol into human breast milk was studied. Two women were treated with labetalol 600 and 1200 mg daily respectively. The milk/plasma ratios were 0.8, 1.1 and 2.6. No consistent relation between milk and plasma concentration in mothers was observed. Therefore the author states that no recommendations could be given concerning the advisability of nursing during labetalol treatment. Measurable plasma concentrations of labetalol, similar to that in the mother, were found only in plasma from one infant where the mother was treated with the dose of 600 mg labetalol per day. No adverse effects were observed in this nursing infant (2).

In twenty-five women (3) labetalol was used for 6 days up to 12 weeks in treatment of severe hypertension during pregnancy. Milk to plasma ratios on day three post partum were 0.22-0.45 with doses from 330 mg/day to 800 mg/day. One patient with a dose of 1200 mg daily had a ratio of 1.87 but she did not breast-feed.

In another article it is stated that labetalol enters breast milk but its concentration is still only 25-50 per cent of that found in maternal plasma appearing not to be sufficient to have any effect on the breast-feeding infant (4).

In one pharmacological handbook (5) it is concluded that the risk to the suckling infant of administering labetalol to its mother is low on the basis that the quantity of drug that passes into milk is small (0.1-0.3 per cent). Breast-feeding is here regarded as safe.

Considering the prematurity of the baby, the clearance of the drug may be reduced until the baby is fully developed. Labetalol is mainly eliminated by glucuronidation. Less than 5 per cent of labetalol is excreted unchanged in urine (6). In two case reports premature children (born in weel 33 and 37) to mothers treated with labetalol during pregnancy, showed symptoms like hypotonia, respiratory disturbances, bradycardia, cyanosis and weak pulses in arteria femoralis. The half-lives of labetalol in these two babies were 5 to 6 times longer compared to adults (7,8).

Professor Rane (9) considers it to be adequate to wait with breast feeding until the baby is fully developed. Thereafter, breast feeding could be regarded as possible although the mother was given a high dose (9). The manufacturer (10) has no further documentation.

Nursing infants to mothers treated with labetalol, especially if the infant is premature, should be closely observed for bradycardia, hypotension, and other symptoms of alpha/beta blockade. Long-term effects of exposure to labetalol from milk have not been studied. The American Academy of Pediatrics considers labetalol to be compatible with breast-feeding (11). In one pharmacological handbook (12) it is said that small amounts of drug ingested by the nursing infant is unlikely to produce any adverse effects.

Like other calcium antagonists felodipine passes into breast milk. However, data suggest that a fully developed child will be exposed to only small amounts of drug and that there should be no risk during breast-feeding (13,14). Felodipine is eliminated by oxidation in the liver to inactive metabolites. No unchanged drug could be found in the urine (12). Careful observations should be considered in premature infants with an undeveloped elimination capacity, and whose mothers had been treated with felodipine. Also a dose reduction should be considered in these premature infants.

Conclusion

Data indicate that labetalol does appear in breast milk. There seems to be large inter- and intraindividual variations with regard to the milk/plasma ratios. However, only a small amount of administered dose is recovered in breast milk. In the present case the benefit of labetalol use in nursing mothers should outweigh the potential risk.

Also small amounts of given felodipine dose passes into breast milk. The risk for the fully developed nursing infant with therapeutic doses is considered small.

Dalen P

References

  1. Briggs, Drugs in pregnancy and lactation, 1994; 4th ed: 477-478
  2. Lunell NO, Kulas J, Rane A: Transfer of labetalol into amniotic fluid and breast milk in lactating women. Eur J Clin Pharmacol 1985; 28: 597-599
  3. Michael CA: Use of labetalol in the treatment of severe hypertension during pregnancy. Br J Clin Pharmacol 1979; 8: 211S-S15S
  4. Leitz FH, Bariletto S, Jaworsky L et a: Secretion of labetalol in breast milk of normotensive lactating women. Presented at the 67th annual meeting of The Federation of American Societies for Experimental Biology, Chicago, April 10-15, 1983
  5. Bennett, Drugs and human lactation, 1988; page
  6. Dollery, Therapeutic drugs. 1991
  7. Haraldsson A, Geven W: Half-life of maternal labetalol in a premature infant. Pharmaceut Weekblad 1989; 11: 229-231
  8. Haraldsson A, Geven W: Severe adverse effects of maternal labetalol in a premature infant. Acta Paediatr Scand 1989; 78: 956-958
  9. Personal communication with professor Anders Rane, Dpt of Clinical Pharmacology, Akademiska sjukhuset, Uppsala
  10. Personal communication with the manufacturer, Glaxo Wellcome, Anne-Catherine Edgren
  11. Briggs, Drugs in pregnancy and lactation, 1994; 4th ed: 477-478
  12. Dollery, Therapeutic drugs, 1991; 1st ed:
  13. Drugline nr 07666 (year 1991)
  14. Drugline nr 09835 (year 1993)

Senast ändrad 2018-09-20